This invention relates to compositions useful as intermediates in the synthesis of herbicides. More particularly, the invention relates to 1,4-diisopropyl-2, 5-diketopiperazine, which has been found to be especially advantageous as an intermediate in the preparation of N-isopropylglycine, a precursor of the herbicide N-phosphonomethylglycine.
N-phosphonomethylglycine, known also by its common name glyphosate, is a highly effective and commercially important phytotoxicant useful in controlling a large variety of weeds and crops. It is applied to the foliage of a very broad spectrum of perennial and annual grasses and broad-leafed plants. Industrial uses include control of weeds along roadsides, waterways, transmission lines, in storage areas, and in other nonagricultural areas. Usually glyphosate is formulated into herbicidal compositions in the form of its various salts which retain the anionic form of glyphosate in solution, preferably in water.
Because of its commercial importance, many processes for making glyphosate have been published. One conventional process for the manufacture of glyphosate is described by Hershman in U.S. Pat. No. 3,969,398. In that process, iminodiacetic acid is reacted with formaldehyde and phosphorous acid to produce an intermediate N-phosphonomethyliminodiacetic acid. This intermediate is oxidized to produce glyphosate.
Another process for the manufacture of glyphosate is described by Gaertner in U.S. Pat. No. 3,927,080. Gaertner describes the production of glyphosate wherein N-t-butyl-N-phosponomethylglycine or its esters are hydrolyzed under acidic conditions. In the process of Gaertner, t-butylamine is reacted with a bromoacetate ester to produce an ester of N-t-butylglycine, which is in turn reacted with formaldehyde and phosphite esters to produce the esters of the N-t-butyl-N-phosphonomethylglycine intermediate.
European Pat. No. 0,055,695 discloses a process for splitting off a substituent group from the nitrogen atom of an N-substituted N-phosphonomethyl-glycine by hydrogenolysis. The N-substituent is described as a 1-arylalkyl group suitable for hydrogenolytic cleavage. The hydrogenolytic process is carried out in the presence of a catalyst such as platinum or palladium on barium sulfate.
Pfleigel et al U.S. Pat. No. 4,065,491 describes a process in which glycine is reacted with formaldehyde and a phosphite ester to produce an ester of glyphosate. Ehrat U.S. Pat. No. 4,237,065 describes a process generally similar to that of the Pfleigel patent.
In the copending and coassigned application of Miller et al, Ser. No. 687,404, filed Dec. 28, 1984, a process is described in which glyphosate is prepared by dealkylation of N-isopropylglyphosate. This has been found to be a particularly effective process for the preparation of glyphosate in relatively high yields. It has been determined, moreover, that the precursor N-isopropylglyphosate may be prepared by phosphonomethylation of N-isopropylglycine. Methods are known for the phosphonomethylation of N-alkylglycines by reaction with formaldehyde and phosphorous acid. The copending and coassigned application of Miller et al. Ser. No. 778,958, filed Sept. 23, 1985 describes a process in which an N-acetyl-N-alkylglycine is phosphonomethylated by introducing both formaldehyde and phosphorous acid into a single reaction pot, without any isolation of the product of the hydrolysis of the acetyl group. According to the latter process, the N-alkyglyphosate also can be dealkylated to glyphosate without prior isolation.
A need, therefore, exists for additional intermediates which can be effectively and economically converted to N-alkylglycines, most particularly N-isopropylglycine, as part of the synthesis of N-alkylglyphosates and glyphosate itself.
A variety of 1,4-disubstituted 2,5-diketopiperazines are known to the art, and are recognized to be useful for various purposes. Thus, for example, Chan et al U.S. Pat. No. 4,140,791 discloses the use of 1,4-di(2,6-dimethylphenyl)-2,5-diketopiperazine for control of various fungal diseases. Sut et al, "N-Monoalkylation of Some 2-Oxo and 2,5-Dioxopiperazines", Chimie Therapeutique, 4 (3), 167-173 (1969), describe the syntheses of a series of 2-oxopiperazines and 2,5-dioxopiperazines which were found to have analgesic and anesthetic activities. Among the specific compounds disclosed by Sut et al are 2,5-diketopiperazines and 3-substituted-2,5-diketopiperazines which are monoor dialkylated at an N- position, or N,N' positions, with ethyl, benzyl, hydroxyethyl, or acetoxyethyl. Other references contain specific disclosure of 1,4-dimethyl-2,5-diketopiperazine, 1,4-diethyl-2,5-diketopiperazine, 1,4-diphenyl-2,5-diketopiperazine, and 1,4-dibenzyl-2,5-diketopiperazine; but it is believed that none of these references disclose the use of such compounds in the preparation of glyphosate or glyphosate precursors.
Okawara et al, "Convenient Syntheses of Piperazine-2,5-Diones and Lactams from Halocarboxamides Using Phase Transfer Catalysts", Chemistry Letters, 1981, pp. 185-188 shows the syntheses of various 1,4-disubstituted 2,5-diketopiperazines by intermolecular condensation of halocarboxamides using a reaction system comprising a mixture of dichloromethane and 50% aqueous sodium hydroxide solution in the presence of a solid phase transfer catalyst. Among the compounds whose syntheses are reported in Okawara et al are 1,4-dibenzylpiperazine-2,5-dione, 1,4-diphenylpiperazine-2,5-dione, and 1,4-diphenyl-3,6-dimethylpiperazine-2,5-dione. The reference does not report any use for the products synthesized.
Cavicchioni et al, "Base-promoted Reactions of .alpha.-Halogeno-alkylanilides", J. Chem. Soc. Perkin Trans. I, pp. 2969-2972 (1982) reports the preparation of both N,N'-dialkylpiperazines and 2-amino-2-haloalkyloxazolidones by intermolecular condensations of the same reactants used in the syntheses described by Okawara et al. Cavicchioni et al do not give much detail on the reaction system utilized, but apparently employed a polar organic solvent system rather than a two phase system comprising a phase transfer catalyst.
Wong et al U.S. Pat. No. 4,400,330 describes the preparation of bis-phosphonomethyl-2,5-diketopiperazine by phosphonomethylation of 2,5-diketopiperazine, followed by hydrolysis of the bis-phosphonomethyl-2,5-diketopiperazine to produce glyphosate. In the phosphonomethylation, formaldehyde and glacial acetic acid are added to 2,5-diketopiperazine to produce a suspension which is refluxed. Thereafter, phosphorus trichloride is added to the reaction mixture which is then maintained at reflux until all of the hydrogen chloride by-product has been driven off. After additional refluxing of the reaction slurry, the product is dried in vacuo, dissolved in water, and treated sequentially with caustic solution and mineral acid to effect hydrolysis and produce glyphosate.